A low east-west mountain range in the state of Zacatecas divides the plateau into northern and southern sections. These two sections, called the Northern Plateau (Spanish: Mesa del Norte) and Central Plateau (Spanish: Mesa Central), are now generally regarded by geographers as sections of one plateau.

While the plateau stretches from north to south, the southern east-west arc of the Central Mexican Plateau from Jalisco to Veracruz states historically as well as today has served as the population nexus of the Mexican nation, it is home to its biggest metro areas of Guadalajara, Leon, Querétaro, Morelia, Mexico City, Toluca, Cuernavaca, and Puebla.

The Mesa Central or southern plateau is higher than its northern counterpart, averaging 2,000 m (6,600 ft) in elevation. The southern plateau contains numerous valleys originally formed by ancient lakes. It extends across the states of Aguascalientes, Jalisco, Zacatecas, Guanajuato, Querétaro, Michoacán, México, and Hidalgo plus the Federal District. Several of Mexico's most prominent cities, including Mexico City and Guadalajara, are located in the valleys of the southern plateau. Much of the southern plateau is drained by the Río Grande de Santiago and its tributaries, including the Río Lerma, which drain west into the Pacific Ocean. Tributaries of the Río Pánuco drain the eastern portion of the southern plateau. The Central Mexican matorral covers much of the southern plateau, with the subtropical Bajío dry forests occupying the lower portions of the Lerma–Río Grande de Santiago basin. Higher altitudes are covered by Mixed Forests, then Temperate Coniferous Forests, up to the snow line in the top of the volcanoes that surround the southern and western edges.